The major long term objective of this proposal is to give the candidate the skills and background to develop an independent research program. The main skills to be developed will be those related to laboratory investigations, but to keep the research clinically relevant and to enable the candidate to train future medical scientists, clinical and teaching skills will also be developed and maintained. The aim of the research proposal is to gain a better understanding of the basic pharmacological regulators that control the resistive and elastic properties of the lung periphery. Preliminary studies indicate the presence of tonic Beta sympathetic dilator activity from circulating catecholamines. Why tonic Beta activity is present and what factors modulate its input provide the major thrust of this proposal. We will administer Beta agonists and antagonists both systemically and locally to sublobar regions of the lung while measuring changes in total lung compliance, total lung resistance, collateral resistance, and local time constants. We will test whether the tonic Beta activity is due to Alpha adrenergic, muscarinic or humoral activity or due to changes in perfusion or in response to cold air. We will test if alterations of sex hormone levels affects Beta receptor activity and number. Because most work on the control of airway tone has concentrated on central airways and because central and peripheral lung respond differently, we will measure parameters of both central and peripheral resistance and compliance whenever possible. Perhaps it is ironic that although most previous work on the autonomic system of the lung has centered on the parasympathetic system, the major therapeutic agents used in treating obstructive disease are the Beta agents. Studies in this proposal will provide insight into the role of the autonomic nervous system, primarily the Beta system in pulmonary disease.